The objective of the proposed study is to use the mouse as a cytogenetic tool to investigate three questions: 1. Are there linkage homologies between mammals, especially between man and mouse? This part of the study will concentrate on finding out whether there are chromosomal banding pattern similarities between several mammalian species, including man, rat, and mouse, for regions or entire chromosomes where genetic homologies are expected, and whether a common X-chromosome can be constructed using several mammalian species known to have X-linked homologies. 2. What is the mechanism of X-chromosomal inactivation? This part of the study will concentrate on determining whether one or more sites are located on the X-chromosome that are responsible for X-inactivation. The levels of proteins coded for by X-linked genes will be determined and chromosomal DNA synthesis patterns will be studied in female mice carrying various reciprocal X-A translocations. These findings will be related to the finding of these same types of translocations in man. 3. What is the relationship between gene-dosage and gene-product? The levels of specific proteins and isozyme patterns will be studied in mice trisomic for genes known to code for these proteins. BIBLIOGRAPHIC REFERENCES: Eicher, E. M., R. H. Stern, J. E. Womack, M. T. Davisson, T. H. Roderick, and S.C. Reynolds. 1976. Evolution of mammalian carbonic anhydrase loci by tandem duplication: Close linkage of Car-1 and Car-2 to the centromeric region of Chromosome 3 of the mouse. Biochem. Genetics: In Press.